With almost 40,000 described species, spiders are second only to insects as the most diverse group of animals on land. In attaining this diversity, spiders have evolved sophisticated chemical weapons, which makes them an attractive target for chemical prospecting. Recent drug candidates developed from spider venom components block the neuronal nicotinic acetylcholine receptor, increase parathyroid hormone (PTH) secretion and inhibit atrial fibrillation, the most common chronic cardiac arrhythmia.
Spider venoms, like those of other venomous animals, consist of complex mixtures of biologically active compounds. The primary small-molecule toxins are often acylpolyamines (with over one hundred structures having been described), though the venom may also contain nucleosides, polypeptides, proteins (including enzymes) as well as citric acid, monoamines and free amino acids.
Considering the large amount of analytical work on spider venom already published, the recent identification of a member of an entirely new class of spider neurotoxin seemed surprising. Activity-guided screening of the venom of the grass spider, Hololena curta, led to the discovery of the unique venom component HF-7, which is a bis-sulfated glyconucleoside. HF-7 has the uncommon ability to effectively block kainate receptors, in addition to weakly blocking L-type calcium channels.
The discovery of this entirely unexpected natural product suggested that spider venoms might still harbor interesting new classes of neurotoxins. Moreover, considering the multitude of acylpolyamines that can be identified from a single species, it seemed unlikely that HF-7 is the only spider venom component of its kind. The question remains why sulfated nucleosides have not been found in any other previous analysis.
An understanding of the neurotoxins contained within the venom and its mode of action can assist in the development of new therapeutic agents. There is a present need to develop a new class of therapeutic agents based on the neurotoxins elucidated from spider venom.